Three-dimensional reconstruction of colon carcinoma metastases in liver
Three-dimensional reconstruction of colon carcinoma metastases in liver
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DOI：
10.1046/j.1365-2818.1997.2140770.x
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发表时间：
1997-07-01
影响因子：
2
通讯作者：
VanNoorden, CJF
中科院分区：
文献类型：
--
作者：
Griffini, P;Smorenburg, SM;VanNoorden, CJF
结肠癌患者切除肝转移瘤可提高生存率，但成功与否取决于切除所有肿瘤组织。为此，了解转移和肝脏结构之间的空间关系至关重要。由于转移性癌症的生长本质上是一个三维（3D）事件，我们决定应用3D重建技术来研究转移与肝脏结构（如血管、基质和肝包膜）之间的空间关系。通过门静脉注射结肠癌细胞CC531，诱导大鼠肝脏发生结肠癌转移。三周后，从这些动物和对照动物的肝脏中取出肝脏，并立即冷冻在液氮中。8个肝脏26个转移灶，每次3D重建使用37 ~ 110个连续切片。用（免疫）组织化学方法对不同结构的轮廓进行染色，在每个切片中进行追踪并存储在数据库中。由轮廓模型生成体模型。在26例转移瘤中，发现有7例离肝包膜较远。它们很小，由分化良好的癌细胞组成，完全被基底膜和基质包围，基底膜和基质总是与门静脉的邻近血管相连。其余19例转移灶表现出更晚期的发展模式。低分化结肠癌细胞通过基质在不同部位浸润，经常发现癌细胞与肝细胞直接接触的区域。这种类型的癌细胞只在转移瘤与肝包膜接触时才会出现，然而，这些晚期的部分区域仍然类似于小的转移瘤。基于这些发现，我们得出结论，基质影响癌细胞的分化模式，并且在肿瘤生长中至少具有双重作用。一方面，它限制了癌细胞对周围宿主组织的侵袭。另一方面，包膜处主要由肉芽组织组成的间质有利于肿瘤的生长。此外，我们的3D重建显示了较大转移瘤的空间异质性，以及3D方法对了解转移瘤的生长和发展的重要性，特别是在肝脏中的结肠癌转移。
Resection of liver metastases in patients with colon cancer increases survival but success depends on removal of all tumour tissue. For this purpose, understanding of spatial relationships between metastases and liver architecture is essential. Because metastatic cancer growth is essentially a three-dimensional (3D) event, we decided to apply 3D reconstruction techniques to study these spatial relationships between metastases and liver structures such as blood vessels, stroma and the liver capsule (Glisson's capsule). Colon carcinoma metastases were experimentally induced in rat liver by injection of colon cancer cells (CC531) into the portal vein. Three weeks later, livers from these animals and control livers were removed and immediately frozen in liquid nitrogen. Thirty-seven to 110 consecutive sections were used for each 3D reconstruction of 26 metastases in eight livers. Contours of different structures were stained by (immuno)histochemical means, traced in each section and stored in a database. From the contour model, a volume model was generated. Among the 26 metastases, seven were found to grow distantly from the liver capsule. They were small and consisted of well-differentiated cancer cells that were totally surrounded by a basement membrane and stroma which was always connected with adjacent blood vessels of a portal tract. The remaining 19 metastases showed a more advanced pattern of development. Infiltration of poorly differentiated colon cancer cells progressed through the stroma at various sites and areas of direct contact between cancer cells and hepatocytes were frequently found. This type of outgrowth of cancer cells was only found when metastases had made contact with the liver capsule, However, some areas in sections of these advanced stages still resembled small metastases. On the basis of these findings, we conclude that stroma affects the differentiation pattern of cancer cells and has at least a dual role in tumour growth. On the one hand it limits invasion of cancer cells in the surrounding host tissue. On the other hand, stroma formation at the capsule, which consists mainly of granulation tissue, facilitates outgrowth of the tumours. Furthermore, our 3D reconstructions demonstrate the spatial heterogeneity of larger metastases and the importance of a 3D approach to understand growth and development of metastases in general and colon cancer metastases in the liver in particular.